The first step to the diagnosis of an organ trouble caused by alcohol is to know an accurate drinking history, but alcohol dependence is called a denying disease, namely, an inveterate drinker does not accurately report his (or her) alcohol intake in all ages and countries. Therefore, an objective marker for substantiating the alcohol intake is necessary. A marker for the habit of drinking most commonly measured is γ-GTP (GGT). However, even if a drinker has a high GGT level, the GGT level does not always correlate with the degree of seriousness of liver trouble or the cumulative alcohol intake of the drinker. In addition, the change of GGT level after alcohol drinking is dependent on individuals and there are a considerable number of so-called nonresponders who show no GGT increase even after drinking a large amount of alcohol.
On the other hand, by a cause other than drinking, GGT is often increased also in a person having no drinking habit, such as a person having fatty liver due to fatness or a person who habitually takes a certain medicine. Guidance is often given, for example, in a hospital for complete physical examination so that a person having a high GGT level may be hastily judged to be a drinker. Therefore, chain-deficient transferrin (CDT) has been developed by investigators in north Europe for examination complementary to the examination with GGT, and its usefulness is emphasized in European and American references. But, in the case of the result obtained for Japanese, CDT as a marker of drinking permits detection of only about 10% of the GGT nonresponders.
Acetaldehyde, the first metabolite of ethanol is so reactive that it forms various acetaldehyde adducts of various proteins. For example, attempts have been made to detect an acetaldehyde-hemoglobin adduct by HPLC or the like. There is also an adduct that is expected to be an interesting marker capable of permitting estimation of alcohol intake in the past, such as HbAlc in the case of diabetes. But, such an adduct has not been put to practical use because of its low sensitivity.
The habit of drinking is one of two major causes of chronic liver troubles. As to liver cirrhosis cases in Japan, the percentage of cases due to only alcohol itself is considered to be only 10 to 15%. This, however, is data obtained mainly in university hospitals and the like. Considering the presence of alcoholics in a number estimated at more than 2,000,000, it is speculated that there are many latent patients with alcoholic liver trouble who have no chance to get a medical examination in a medical institution. In addition, since the habit of drinking is a factor of the exacerbation of cerebral hemorrhage, hypertension, gout and the like, early and accurate screening of problem drinkers is very important. However, as described above, there is no marker having decisive sensitivity and specificity among existing so-called markers of drinking, and hence searching for a novel marker is desired.
A general method for comprehensive expression protein analysis is two-dimensional protein electrophoresis, but this method is disadvantageous in the detection of low-molecular weight proteins or peptides. In recent years, a protein chip technology comprising a combination of surface enhanced laser desorption ionization (SELDI) and a time-of-flight mass spectrometer has been developed by Ciphergen Biosystems Inc., USA and has been begun to be clinically used for, for example, detecting a novel tumor marker. Therefore, comprehensive search for a novel marker by the utilization of such a proteomics technique and the like is desired.